Complement inhibitors in myocardial ischemia/reperfusion injury.
Myocardial ischemia/reperfusion injury is accompanied by an inflammatory response contributing to reversible and irreversible changes in tissue viability and organ function. Endothelial and leukocyte responses are involved in tissue injury, orchestrated primarily by the complement cascade. Anaphylatoxins, and assembly of the membrane attack complex contribute directly and indirectly to further tissue damage. Tissue salvage can be achieved by depletion of complement components, thus making evident a contributory role for the complement cascade in ischemia/reperfusion injury. The complexity of the complement cascade provides numerous sites as potential targets for therapeutic interventions designed to modulate the complement response to injury. The latter is exemplified by the ability of a soluble form of complement receptor 1 (sCR1) to decrease infarct size in in vivo models of ischemia/reperfusion injury as well as prevent myocyte and vascular injury and organ dysfunction by interdicting assembly of the membrane attack complex. Effective inhibitors of complement are not limited to newly developed compounds or solubilized forms of endogenous regulators of complement activation. Therapeutic agents in common use, such as heparin and related non-anticoagulant glycosaminoglycans, are known to inhibit the complement activation in vitro as well as in vivo and may prove useful as cytoprotective agents.
Lucchesi
B R
BR
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA. benluc@umich.edu
Kilgore
K S
KS
D000706:Anaphylatoxins / Q000276:immunology*; D000818:Animals; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D006025:Glycosaminoglycans / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D017202:Myocardial Ischemia / Q000276:immunology* / Q000473:pathology; D011817:Rabbits; D011951:Receptors, Complement / Q000187:drug effects / Q000276:immunology; D015427:Reperfusion Injury / Q000276:immunology*; D014655:Vascular Resistance / Q000276:immunology
D000706:Anaphylatoxins; D000933:Antifibrinolytic Agents; D015938:Complement Membrane Attack Complex; D006025:Glycosaminoglycans; D011951:Receptors, Complement; D006493:Heparin